TY - JOUR
T1 - Evaluation of Pseudomonas aeruginosa staphylolysin (LasA protease) in the treatment of methicillin-resistant Staphylococcus aureus endophthalmitis in a rat model
AU - Barequet, Irina S.
AU - Habot-Wilner, Zohar
AU - Mann, Oran
AU - Safrin, Mary
AU - Ohman, Dennis E.
AU - Kessler, Efrat
AU - Rosner, Mordechai
N1 - Funding Information:
Acknowledgements Supported by grants from the Maratier Foundation for the study of Blindness and Visual Disorders of the Tel Aviv University Sackler Faculty of Medicine (ISB and EK), the Tel Aviv University Foundation for Basic Research (EK), Public Health Service grant AI 26187 from the National Institute of Allergy and Infectious Diseases (DEO) and in part by Veterans Administration Medical Research Funds (DEO).
PY - 2009
Y1 - 2009
N2 - Background: Therapy of S. aureus ocular infections is increasingly challenging due to emerging resistant strains. Staphylolysin (also called LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of this study was to evaluate the efficacy of staphylolysin as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis, focusing on its bactericidal activity. Methods: Endophthalmitis was induced in the right eyes of 46 rats by an intravitreal injection of 50-160 MRSA cells. Two therapeutic regimens were evaluated: (i) an intravitreal injection of staphylolysin at 6 hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at 6 and 30 hours post-infection. Control eyes were injected with vehicle alone at the same times. The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU). Potential adverse effects of intravitreal staphylolysin injection were assessed histopathologically in four uninfected eyes, enucleated from rats sacrificed 1 month after intravitreal staphylolysin injection. Results: In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous threefold as compared to control (2,055±3,144 and 6,432±6,389 CFU/vitreous, respectively; P=0.02). The repeated injection protocol was more effective, reducing the mean CFU value per vitreous by two orders of magnitude as compared to control (1,148±3,096 and 143,519±151,358 CFU/vitreous, respectively; P=0.0005). Histopathological analysis showed no structural damage in eyes injected intravitreally with staphylolysin. Conclusions: Staphylolysin is effective in the treatment of experimental MRSA-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of S. aureus endophthalmitis in humans.
AB - Background: Therapy of S. aureus ocular infections is increasingly challenging due to emerging resistant strains. Staphylolysin (also called LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of this study was to evaluate the efficacy of staphylolysin as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis, focusing on its bactericidal activity. Methods: Endophthalmitis was induced in the right eyes of 46 rats by an intravitreal injection of 50-160 MRSA cells. Two therapeutic regimens were evaluated: (i) an intravitreal injection of staphylolysin at 6 hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at 6 and 30 hours post-infection. Control eyes were injected with vehicle alone at the same times. The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU). Potential adverse effects of intravitreal staphylolysin injection were assessed histopathologically in four uninfected eyes, enucleated from rats sacrificed 1 month after intravitreal staphylolysin injection. Results: In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous threefold as compared to control (2,055±3,144 and 6,432±6,389 CFU/vitreous, respectively; P=0.02). The repeated injection protocol was more effective, reducing the mean CFU value per vitreous by two orders of magnitude as compared to control (1,148±3,096 and 143,519±151,358 CFU/vitreous, respectively; P=0.0005). Histopathological analysis showed no structural damage in eyes injected intravitreally with staphylolysin. Conclusions: Staphylolysin is effective in the treatment of experimental MRSA-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of S. aureus endophthalmitis in humans.
KW - Endophthalmitis
KW - LasA protease
KW - Rat model
KW - Staphylococcus aureus
KW - Staphylolysin
UR - http://www.scopus.com/inward/record.url?scp=67349162642&partnerID=8YFLogxK
U2 - 10.1007/s00417-009-1061-2
DO - 10.1007/s00417-009-1061-2
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AN - SCOPUS:67349162642
SN - 0721-832X
VL - 247
SP - 913
EP - 917
JO - Graefe's Archive for Clinical and Experimental Ophthalmology
JF - Graefe's Archive for Clinical and Experimental Ophthalmology
IS - 7
ER -
